DESCRIPTION: Ultrafiltration probes will be developed to quantify secretion of hormones and cytokines such as leptin and TNF-a from adipose tissue in order to study the mechanisms underlying the development of obesity and its associated pathologies. Probes will be designed to optimize quantification of cytokine secretion from subcutaneous adipose tissue using the pig as an experimental model. Initial experiments will involve validation of the recovery and stability of leptin and TNF-a taken up by the ultrafiltration probe in vitro. Additionally, the probe characteristics and packaging will be optimized for long-term sampling in the pig. Ultrafiltration probes will then be tested in vivo in pigs under conditions which will physiologically alter the level of expression of leptin and TNF-a in adipose tissue: fasting and lipopolysaccharide administration. Upon validation of the appropriateness of ultrafiltration technology for measuring the secretion of molecules from adipose tissue, probes will be developed to measure other adipose tissue-secreted proteins and to test the effects of anti-obesity and anti-diabetes drugs on adipocytic function and protein secretion. These probes will serve as valuable tools for academic and industrial research leading to new drug/therapy discovery. PROPOSED COMMERCIAL APPLICATION: The economic impact of the system we are developing comes from the central role obesity plays in the health of a aging population. There are many incentives to conduct basic research into the mechanisms of obesity and applied research for pharmaceuticals to control obesity and the pathological complications of obesity. The products we are developing would find widespread commercial application in this emerging field. Because of the central role obesity plays int he health of a aging population, there are many incentives to study obesity. The probes being developed in this project will be marketed for basic research into the mechanisms of obesity and for pharmaceutical and other research to prevent and control the pathological complications of obesity.